Arnaldo Foradori

Urinary vasodilator and vasoconstrictor angiotensins during menstrual cycle, pregnancy, and lactation

Since normal human pregnancy is characterized by normotension in the face of an increased renin-angiotensin-aldosterone system (RAAS), we evaluated the temporal pattern of urinary excretion of a novel vasodilator within this system, angiotensin-(1–7) (Ang-[1–7]), during the menstrual cycle, pregnancy, and lactation. The urinary profiles of Ang I, Ang II, human chorionic gonadotropin, 17β-estradiol, and progesterone were also determined. During the menstrual cycle, urinary Ang-(1–7) and Ang II remained stable (mean cycle value: 94.6±11.3 and 11.4±1.1 pmol/g of creatinine, respectively) in nine females. In 10 normal pregnant women, urinary Ang-(1–7) and Ang II increased throughout gestation, averaging 1499.8±310 and 224.4±58 pmol/g of creatinine, respectively (p<0.05) at wk 35 and falling during lactation to 394.0±95 and 65.7±20 pmol/g of creatinine (p<0.05), respectively. The Ang-(1–7)/Ang II ratio was unchanged in the different reproductive periods. During the menstrual cycle, Ang II and Ang-(1–7) correlated with 17β-estradiol and progesterone using multivariate analysis (r=0.31, p<0.001) and r=0.28, p<0.02, respectively). During gestation, 17β-estradiol and progesterone correlated with urinary Ang-(1–7) (r=0.48, p<0.001 and r=0.47, p<0.001, respectively) and Ang II (r=0.24, p<0.03 and r=0.25, p<0.03, respectively); by multiple regression, only Ang-(1–7) correlated with both steroids (r=0.49, p<0.001). The progressive rise of Ang-(1–7) throughout gestation, probably modulated by estrogen and progesterone, suggests a physiologic counterregulation within the RAAS.

Response of the Maternal, Fetal, and Neonatal Pituitary-Thyroid Axis to Thyrotropin-Releasing Hormone!

Abstract: Thyrotropin releasing hormone (TRH) readily crosses the placenta and stimulates the fetal pituitary. We studied the response of the maternal and fetal pituitary-thyroid axes to TRH and the influence of prenatal exposure to TRH on the physiological postnatal increase in thyrotropin (TSH) and triiodothyronine (T3) in the neonate. Twenty-six pregnant women received TRH (400 or 600 μng) intravenous or saline (controls) either 2 or 12 h before elective cesarean section at term. Administration of 400 jug of TRH resulted in significant elevations of maternal TSH (15.7 ± 2.9 versus 3.2 ± 0.4 μU/ml, p < 0.01) and prolactin (416 ± 94 versus 223 ± 41 ng/ml, p < 0.05) 2 h later. Maternal T3 remained unchanged. A higher dose of TRH (600 μg) produced comparable results. Maternal administration of TRH (400 μg) 2 h before delivery resulted in significant increases in fetal TSH and T3 over controls (21.1 ± 3.7 versus 4.8 ± 1.0 μU/ml, and 132 ± 12 versus 64 ± 9 ng/dl, p < 0.01, respectively). Cord blood hormone levels 12 hours after TRH administration were similar to controls. Higher doses of TRH did not produce further increases in fetal TSH or T3. Control and treated neonates demonstrated similar physiological postnatal increases in TSH and T3, suggesting that prior exposure to TRH did not blunt this response. These data suggest that maternal administration of TRH is an effective way of increasing fetal T3 levels, and that this treatment does not inhibit the postnatal surge in TSH and T3.

An alternative ELISA for T4 determination based on idiotype anti-idiotype interaction and a latex method for anti-idiotype monoclonal antibody selection

This paper is the first report on the use of an idiotype-anti-idiotype monoclonal antibody reaction to develop an enzyme immunoassay for thyroxine (T4). We have developed a monoclonal antibody against T4, named 1F10 of IgG1 subclass and KA 5.21 x 10(8) M-1 which was used to obtain anti-idiotypic monoclonal antibodies. Anti-idiotypic antibodies were selected by a novel method, a passive agglutination assay with the idiotype monoclonal 1F10 absorbed on latex particles and subsequently characterized by RIA. One of these anti-idiotype antibodies, named 5B3--type beta antibody--of IgG1 subclass, was used to develop an enzyme-linked T4 idiotype-anti-idiotype immunosorbent assay. The T4 calibration curve, using the 1F10 idiotypic antibody adsorbed to solid phase and the 5B3 anti-idiotypic antibody conjugated to alkaline phosphatase (ALP), shows adequate performance in the range between 0.7-25 micrograms% of the analyte. The reliability of the proposed method is demonstrated by the correlation coefficient r = 0.74, found between T4 measured by RIA and our assay, with a panel of sera from euthyroid, hypothyroid and hyperthyroid individuals. The correlation coefficient was r = 0.93 within assays and r = 0.88 between assays. These results provide the basis for a new non isotopic assay for the study and diagnosis of T4-related human disease and provides a model to develop immunoassays for other haptens and small molecules of clinical interest.

Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis

We evaluated the response of preterm fetuses to maternal intravenous injection of 400 micrograms of thyrotropin releasing hormone (TRH) between 30 minutes and 5 hours before delivery (n = 12). An additional seven mothers received saline solution and served as control subjects. There were no statistically significant differences in gestational age, birth weight, or Apgar scores between groups. At delivery, concentrations of maternal thyrotropin were elevated in the TRH group compared with the control group (12.0 +/- 1.6 vs 5.6 +/- 0.5 mU/L; p less than 0.005); however, maternal triiodothyronine (T3) values remained unchanged. Significant elevations of fetal thyrotropin and T3 were observed after maternal administration of TRH compared with control subjects (45.8 +/- 7.7 vs 8.4 +/- 0.9 mU/L (p less than 0.002) and 1.3 +/- 0.07 vs 0.7 +/- 0.04 nmol/L or 87 +/- 5 vs 49 +/- 3 ng/dl (p less than 0.001), respectively). Fetal thyroxine (T4) and prolactin values were also elevated after exposure to TRH (135 +/- 5 vs 86 +/- 10 nmol/L or 10.5 +/- 0.4 vs 6.7 +/- 0.8 micrograms/dl (p less than 0.001) and 212 +/- 31 vs 105 +/- 28 micrograms/L (p less than 0.05), respectively). Two hours after birth, a significant increase in T3 but not T4 levels was observed in both groups of infants. These data indicate that fetal exposure to a single dose of TRH via maternal administration of this hormone results in marked stimulation of the preterm fetal pituitary-thyroid axis, as in the fetus at term, and that this treatment does not inhibit the early postnatal surge of T3.

Identificación y caracterización del adulto mayor saludable

Aun no existe una definicion operacional de envejecimiento saludable en la practica clinica, pese a ser una meta de las politicas de salud de la OMS. El objetivo de este estudio es desarrollar un protocolo clinico que permita identificar personas mayores saludables en la comunidad, con el fin de estudiar sus caracteristicas clinicas, de laboratorio y funcionalidad. Metodos: Se invito de manera abierta a participar de este estudio a personas mayores saludables. Se considero saludable a individuos mayores de 60 anos, de la comunidad, funcionalmente activos, con baja carga de comorbilidad y que se auto-percibieran saludables. Los participantes fueron entrevistados telefonicamente y aquellos que cumplieron los criterios fueron evaluados mediante una evaluacion geriatrica integral, que incluia evaluacion clinica, antropometrica, funcional (Timed get up and Go), y laboratorio. Resultados: Un total de 384 personas respondieron al llamado y 83 cumplieron los criterios de saludable, 57% mujeres, edad promedio 71 anos (60-98), 78% no consumia ningun medicamento, 100% tenia una capacidad fisica mayor de 3 Mets . El laboratorio basico mostro que cerca del 90% de los sujetos estaba en el rango de normalidad usando los criterios de referencia estandar establecido para poblacion adulta. Conclusiones: Este estudio revela que el protocolo desarrollado fue capaz de identificar personas mayores saludables, con baja carga de comorbilidad y buena funcionalidad. Ademas valida la historia clinica y la valoracion geriatrica integral como instrumento fidedigno para identificar a estos sujetos. Este protocolo podria ser usado para mejorar el conocimiento sobre las caracteristicas propias de un envejecimiento saludable.

470 THYROTROPIN RELEASING HORMONE (TRH) ADMINISTRATION TO PREGNANT WOMEN STIMULATES FETAL T 3 PRODUCTION

Thyroid hormones enhance fetal lung maturation; this effect is synergisttc with that of glucocorticoids. Their potential clinical usefulness for the prevention of RDS is limited by poor transplacental passage. TRH has been reported to cross the placenta and to stimulate the fetal pituitary-thyroid axis. In order to evaluate its effectiveness pregnant women at term were injected with either saline (n=3), TRH (Thypinone, Abbot) 400 μg (n=4), or TRH 600 μg (n=3), 2 h prior to elective cesarean section. Serum levels of TSH, T3 and prolactin were determined by RIA in mothers and neonates. Administration of 400 μg TRH resulted in a 275% increase in maternal TSH levels and a 22% and 75% increase in T3 and prolactin levels, resp. 600 μg of TRH produced a 309% increase in maternal TSH, but no further increase in T3 or prolactin. The cord blood levels in the babies were as follows:All neonates exhibited the normal postnatal surge in T3 and prolactin levels. No side effects were noted in the mothers or infants. Maternal administration of TRH results in a large increase in fetal T3 levels. TRH could potentially be used to accelerate fetal lung maturation in humans.